Epstein-Barr versus (EBV) has an unusual range of biologic behaviour extending from the production of inapparent infection, to infectious mononucleosis (IM), to an intimate association with two human tumors, Burkitt lymphoma and nasopharyngeal carcinoma. The objectives of the proposed program are to explore the complex host-parasite relationships, and pathogenetic mechanisms of EBV infections, using a variety of approaches. These will combine the methods of clinical epidemiology and virology, and biologic and molecular virology. Each of the proposals addresses problems of intrinsic importance which are interrelated in terms of achieving a broad understanding of the biology of EB virus. Investigations will focus on: l) clinical, epidemiologic, and virologic aspects of primary infections in two age groups, viz. young children and college students; 2) identification of the cell type(s) involved in the production of EBV present in oropharyngeal fluids; 3) characterization of the secretory IgA antibody response in IM; 4) examination of subpopulations of lymphocytes and monocytes present in peripheral blood of IM patients in order to characterize the cells which are infected, to determine whether they are transformed or are virocytes, and to investigate the mechanisms by which peripheral lymphocytes from mononucleosis patients transform in vitro; 5) development of methods to probe the manner in which lymphocytes regulate EB virus expression, using viral mutants as tools for analyzing virus functions; and 6) identification of cells harboring latent EBV using electron microscopy and nucleic acid hybridization.